2-chlorohexadecanal derived from hypochlorite-modified high-density lipoprotein-associated plasmalogen is a natural inhibitor of endothelial nitric oxide biosynthesis.

Objective: Myeloperoxidase, a heme enzyme that is present and active in human atherosclerotic lesions, provides a source for the generation of proinflammatory chlorinated reactants contributing to endothelial dysfunction. Modification of high-density lipoprotein (HDL) by hypochlorous acid/hypochlorite (HOCl/OCl-) [correction]-generated in vivo by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes-forms a proatherogenic lipoprotein particle that binds to and is internalized by endothelial cells.

Methods And Results: Here we show that HDL, modified with physiologically relevant HOCl concentrations, attenuates the expression and activity of vasculoprotective endothelial nitric oxide synthase.